Imperial College London

Academic Institute

Clinical Sponsor is not required

Unknown

Yes

NIBDAPC_2025_0044

Cerebral small vessel disease (cSVD) affects the smaller blood vessels in the brain. It is common in older people and is thought to contribute to almost half of all dementia cases and at least one quarter of all strokes. It affects memory and thinking, balance, coordination and mood. Typically, blood flow to particular areas in the brain increases when the area becomes more active. This ensures that the brain gets enough blood at the right place and time. In people with cerebral small vessel disease (cSVD), this process is disrupted, and the increased blood flow in response to activity is decreased or absent. Damage to the endothelial cells is a key pathological process in cSVD. Endothelial cells form the layer that lines the inside of blood vessels, and play a crucial role in controlling blood flow and maintaining blood vessel health. The aim of this study is to find out whether endothelial cell function and blood flow in cSVD can be improved by altering the function of a protein called 18kDa Translocator Protein (TSPO). We will do this by using a drug called XBD173, which binds to TSPO. cSVD patients will be recruited from Imperial College Healthcare NHS Trust. This is a double-blind, randomised, crossover study. This means that each participant receives the drug XBD173 and a placebo at different times, the order of which is decided by chance, and neither the participant nor the researchers know which intervention they are receiving. Participants will be invited to the clinical research facility (CRF) at Hammersmith Hospital and randomised to receive the drug XBD173 or matched placebo, twice daily, for 4 weeks. After a 6-week break where no drug is taken, participants will be switched to receive the other intervention. The study visits will involve MRI scans and blood tests to assess endothelial cell function. Healthy volunteers will also be recruited to help define and optimise the MRI scanning procedure, and provide control images . They will attend for a single MRI scan and not receive the drug XBD173.

Cerebral small vessel disease (cSVD) affects the smaller blood vessels in the brain. It is common in older people and is thought to contribute to almost half of all dementia cases and at least one quarter of all strokes. It affects memory and thinking, balance, coordination and mood. People with cSVD may lose their independence and require care. There is an unmet clinical need for an effective treatment for cSVD. Although cardiovascular risk factors are strongly associated with cSVD, their treatment, which is the current management strategy for cSVD, has little impact on established cSVD. Participants will not gain any personal benefit from this research. However, information from this study could improve our understanding of cSVD and aid the development of more effective treatment.

Public Health Research

11/04/2025

Not applicable

Not applicable

One-off

TRE